Dissertations and Theses

Date of Award


Document Type



Biomedical Engineering

First Advisor

Luis Cardoso


plaque rupture, microcalcifications, numerical modeling, vulnerable plaque, vascular stenting, Vasa Vasorum


Atherosclerotic disease is initiated by cholesterol build-up beneath the endothelium, which evolves into a fibroatheroma, a lipid-rich plaque covered by a fibrous cap. Many of these plaques are considered as vulnerable, as they grow to occlude the luminal section of the artery (chronically stenotic) or become mechanically unstable with a higher chance of rupturing (rupture-prone). On one hand, chronically stenotic vulnerable plaques are symptomatic lesions that are often treated with Percutaneous Transluminal Intervention (PTI). Unfortunately, approximately 10% of PTI procedures are followed by severe Neointima Hyperplasia (NH), which causes a new occlusion and failure of the implant. A significant precursor of NH appears to be PTI-induced vascular hypoxia, but the reason for this drop in oxygen tension remains unclear. On the other hand, rupture-prone vulnerable plaques are predominantly asymptomatic and remain silent until the fibrous cap ruptures under the action of blood pressure, triggering a sudden, severe clinical event such as myocardial infarction or stroke. The stability of the fibrous cap is crucial to assess the vulnerability of a plaque, but a thorough characterization of the factors that compromise its mechanical integrity has yet to be defined.

In this dissertation, we first explored Vasa Vasorum (VV) compression after PTI as the root cause of vascular hypoxia and then analysed the effect of micro-calcifications (µCalcs) as a high-risk indicator of plaque vulnerability. To achieve this, we combined numerical simulations on idealized and ex-vivo human coronary arteries, high-resolution imaging modalities, the development of a micro-material tensile machine, characterization of arterial tissues mimicking materials, and mechanical testing of fibrous caps laboratory models. Overall, we found that PTI significantly deforms the VV network that perfuses the artery, with levels of compressions that depend on the location of the branches and the degree of stent expansion. The VV that are squeezed the most experience major fold-increases in hydraulic resistance, which could lead to vascular hypoxia, followed by NH. We demonstrated that the presence of one spherical µCalc in the cap tissue is the most influential factor of plaque vulnerability together with the cap thickness. The µCalc-induced stress amplification at the particle tensile poles can transform a stable human coronary atheroma into a rupture-prone lesion. The same effect is also observed in fibrous cap laboratory models containing hard solid micro-beads (µBeads). When the µBeads -to-cap model size ratio reaches a critical point, the material starts experiencing early rupture, with a reduction in ultimate strength that is positively correlated with the µBeads diameter. Additionally, closely spaced µBeads further compromise the mechanical stability of the fibrous cap phantoms, validating previous analytical and numerical studies that showed an exponential increase in stresses between close pairs of µCalcs.



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